DEMOGRAPHY OF GENES IN NATURE AND THE LABORATORY

自然界和实验室中的基因人口学

• 批准号: 2002357
• 负责人: MARC TATAR
• 金额: $ 7.22万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2002357
• 关键词: Caenorhabditis elegans; Drosophilidae; aging; animal mortality; animal old age; animal population genetics; developmental genetics

Opinions vary on how genes affect mortality rate. A common view is that genetic variation primarily affects the rate of increase in mortality with age, but recent data suggests that genetic variation primarily affects the initial mortality rate. The proposed research intends to resolve this ambiguity. It will determine for a series of natural populations of grasshoppers and for recently published laboratory populations of invertebrates whether genetic variation affects longevity through variation in the initial mortality rate or the rate at which mortality changes with age. Populations of genetically distinct Melanoplus sanguinipes grasshoppers from the Sierra Nevada, California will be used to represent natural variation in aging. M. Sanguinipes along an altitudinal gradient exhibit ordered differences in adult longevity under sheltered conditions. These differences in survival reflect genetic variation for senescence. The research will determine whether this variation is due primarily to differences in initial mortality rate or in the rate of change in mortality. The project will construct, under common sheltered conditions, large life tables for male cohorts from each of five populations along the gradient. Life tables will be constructed in each of two thermal conditions to control for gene-by- environment interactions. Second generation laboratory offspring will be studied to eliminate variation due to maternal effects. To evaluate the effects of genetic variation in laboratory populations, the research will compile demographic dat for genetic variants of Drosophila melanogaster and Ceonorhabditis elegans published since 1990 and reanalyze these life tables with maximum likelihood and resampling methods. The program addresses a fundamental question about aging in both human and animal model systems: How do genes affect mortality rate? The work will help bridge the demographic and molecular approaches to aging. From this approach we may come to understand the causes for senescence and discover avenues to manage mortality and morbidity.

关于基因如何影响死亡率，人们有不同的看法。 一个共同的观点 基因变异主要影响 但最近的数据表明，遗传变异 主要影响初始死亡率。 拟议研究 他试图解决这种模糊性。 它将决定一系列 蝗虫的自然种群和最近发表的 无脊椎动物的实验室种群是否遗传变异 通过初始死亡率的变化或 死亡率随年龄变化的比率。 种群 在遗传学上不同的Melanoplus sanguinipes蚱蜢， 内华达州、加州的Sierra将用于表示自然变异 在老化。M. 沿着海拔梯度的血足动物展览 在庇护条件下，成年人寿命的差异是有序的。 这些生存差异反映了遗传变异， 衰老这项研究将确定这种变化是否是 这主要是由于初始死亡率或 死亡率的变化。 该项目将建设，在共同的 庇护条件，男性队列的大型生命表， 沿梯度分布沿着分布着五个种群。 将构建生命表 在两种热条件中的每一种中， 环境的相互作用。 第二代实验室后代 将进行研究，以消除由于母体效应而产生的变异。 到 评估遗传变异对实验室种群的影响， 这项研究将收集遗传变异的人口数据， 果蝇和秀丽新小杆线虫发表 并以最大似然法重新分析这些生命表 和恢复方法。 该计划解决了一个基本问题， 关于人类和动物模型系统中的衰老问题： 基因如何影响死亡率？ 这项工作将有助于弥合 从人口学和分子学的角度来研究老龄化。 从这个 我们可能会了解衰老的原因， 探索控制死亡率和发病率的途径。